Effect of Pharmaceutically Acceptable Glycols on the Stability of the Liquid Crystalline Gels Formed by Poloxamer 407 in Water

摘要

The ability of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide)(PEO-PPO-PEO) block copolymers (Poloxamers) to form "gels" (lyotropic liquid crystalline structures) in water is of interest to pharmaceutical applications. In such applications the presence of polar organic solvents is often desirable or required. The effect of such solvents on the stability of lyotropic liquid crystalline gels formed by PEO-PPO-PEO block copolymers was assessed by studying the phase behavior and structure in ternary isothermal (25 deg C) systems of pharmaceutical interest consisting of Poloxamer 407 (EO_100PO_40EO_100), water, and one of the following solvents (referred to here colletively as "glycols"): glycerol, propylene glycol, ethanol, polyethylene glycol 400, and glucose. Small-angle X-ray scattering was employed to establish the structure of the liquid crystals obtained and to determine their characteristic length scales. The stability rang eof the liquid crystalline gel phases in the systems studied was found to vary with the glycol type. For example, the micellar cubic structure can accommodate about 0.85:1 parts glucose per part water (in terms of weight) and up to as much as 5.5:1 parts propylene glycol per part water. A correlation between the glycol effects on the stability of the liquid crystalline phases and glycol physiochemical characteristics such as octanol/water partition co-efficient or solubility parameter is proposed.